Mutations in the c-erbAβ1 gene: do they underlie euthyroid fibromyalgia?

Abstract Fibromyalgia, a chronic condition of widespread pain, stiffness, and fatigue, has proven unresponsive to drugs, the use of which is based on the ‘serotonin-deficiency hypothesis’. An alternative hypothesis—failed transcription regulation by thyroid hormone — can explain the serotonin deficiency and other objective findings and symptoms of euthyroid fibromyalgia. Virtually every feature of fibromyalgia corresponds to signs or symptoms associated with failed transcription regulation by thyroid hormone. In hypothyroid fibromyalgia, failed transcription regulation would result from thyroid-hormone deficiency. In euthyroid fibromyalgia, failed transcription regulation may result from low-affinity thyroid hormone receptors coded by a mutated c-erbAβ 1 gene, yielding partial peripheral resistance to thyroid hormone. The hypothesis of this paper is that, in euthyroid fibromyalgia, a mutant c-erbA β 1 gene (or alternately, the c-erbA α 1 gene) results in low-affinity thyroid-hormone receptors that prevent normal thyroid hormone regulation of transcription. As in hypothyroidism, this would cause a shift toward a-adrenergic dominance and increases in both cyclic adenosine 3′-5′-phosphate phosphodiesterase and inhibitory G 1 proteins. The result would be tissue-specific hypothyroid-like symptoms despite normal circulating thyroid-hormone levels.